Alternating Acquisition Technique for Quantification ofin vitroHyperpolarized [1-13C] Pyruvate Metabolism (original) (raw)
Related papers
Journal of Magnetic Resonance, 2009
1-13 C] pyruvate pre-polarized via DNP has been used in animal models to probe changes in metabolic enzyme activities in vivo. To more accurately assess the metabolic state and its change from disease progression or therapy in a specific region or tissue in vivo, it may be desirable to separate the downstream 13 C metabolite signals resulting from the metabolic activity within the tissue of interest and those brought into the tissue by perfusion. In this study, a spectral-spatial saturation pulse that selectively saturates the signal from the metabolic products [1-13 C] lactate and [1-13 C] alanine was designed and implemented as outer volume suppression for localized MRSI acquisition. Preliminary in vivo results showed that the suppression pulse did not prevent the pre-polarized pyruvate from being delivered throughout the animal while it saturated the metabolites within the targeted saturation region.
2009
1-13 C] pyruvate pre-polarized via DNP has been used in animal models to probe changes in metabolic enzyme activities in vivo. To more accurately assess the metabolic state and its change from disease progression or therapy in a specific region or tissue in vivo, it may be desirable to separate the downstream 13 C metabolite signals resulting from the metabolic activity within the tissue of interest and those brought into the tissue by perfusion. In this study, a spectral-spatial saturation pulse that selectively saturates the signal from the metabolic products [1-13 C] lactate and [1-13 C] alanine was designed and implemented as outer volume suppression for localized MRSI acquisition. Preliminary in vivo results showed that the suppression pulse did not prevent the pre-polarized pyruvate from being delivered throughout the animal while it saturated the metabolites within the targeted saturation region.
Magnetic Resonance in Medicine, 2018
Purpose: For 13 C echo-planar imaging (EPI) with spectralspatial excitation, main field inhomogeneity can result in reduced flip angle and spatial artifacts. A hybrid time-resolved pulse sequence, multi-echo spectral-spatial EPI, is proposed combining broader spectral-spatial passbands for greater offresonance tolerance with a multi-echo acquisition to separate signals from potentially co-excited resonances. Methods: The performance of the imaging sequence and the reconstruction pipeline were evaluated for 1 H imaging using a series of increasingly dilute 1,4-dioxane solutions and for 13 C imaging using an ethylene glycol phantom. Hyperpolarized [1-13 C]pyruvate was administered to two healthy rats. Multiecho data of the rat kidneys were acquired to test realistic cases of off-resonance. Results: Analysis of separated images of water and 1,4-dioxane following multi-echo signal decomposition showed waterto-dioxane 1 H signal ratios that were in agreement with the independent measurements by 1 H spectroscopy for all four concentrations of 1,4-dioxane. The 13 C signal ratio of two coexcited resonances of ethylene glycol was accurately recovered after correction for the spectral profile of the redesigned spectral-spatial pulse. In vivo, successful separation of lactate and pyruvate-hydrate signals was achieved for all except the early time points during which signal variations exceeded the temporal resolution of the multi-echo acquisition. Conclusion: Improved tolerance to off-resonance in the new 13 C data acquisition pipeline was demonstrated in vitro and in vivo.
Journal of Magnetic Resonance, 2015
Magnetic resonance imaging and spectroscopy of hyperpolarized (HP) compounds such as [1-13 C]-pyruvate has shown tremendous potential for new insight into disease and response to therapy. New applications of this technology in clinical research and care will require extensive validation in cells and animal models, a process that may be limited by the high cost and modest throughput associated with dynamic nuclear polarization. Relatively wide spectral separation between [1-13 C]-pyruvate and its chemical endpoints in vivo are conducive to simultaneous multisample measurements, even in the presence of a suboptimal global shim. Multi-channel acquisitions could conserve costs and accelerate experiments by allowing acquisition from multiple independent samples following a single dissolution. Unfortunately, many existing preclinical MRI systems are equipped with only a single channel for broadband acquisitions. In this work, we examine the feasibility of this concept using a broadband multi-channel digital receiver extension and detector arrays that allow concurrent measurement of dynamic spectroscopic data from ex vivo enzyme phantoms, in vitro anaplastic thyroid carcinoma cells, and in vivo in tumor-bearing mice. Throughput and the cost of consumables were improved by up to a factor of four. These preliminary results demonstrate the potential for efficient multi-sample studies employing hyperpolarized agents.
Journal of Magnetic Resonance, 2011
Undersampled spiral CSI (spCSI) using a free induction decay (FID) acquisition allows subsecond metabolic imaging of hyperpolarized 13 C. Phase correction of the FID acquisition can be difficult, especially with contributions from aliased out-of-phase peaks. This work extends the spCSI sequence by incorporating double spin-echo radiofrequency (RF) pulses to eliminate the need for phase correction and obtain high quality spectra in magnitude mode. The sequence also provides an added benefit of attenuating signal from flowing spins, which can otherwise contaminate signal in the organ of interest. The refocusing pulses can potentially lead to a loss of hyperpolarized magnetization in dynamic imaging due to flow of spins through the fringe field of the RF coil, where the refocusing pulses fail to provide complete refocusing. Care must be taken for dynamic imaging to ensure that the spins remain within the B 1 -homogeneous sensitive volume of the RF coil.
2011
Undersampled spiral CSI (spCSI) using a free induction decay (FID) acquisition allows subsecond metabolic imaging of hyperpolarized 13 C. Phase correction of the FID acquisition can be difficult, especially with contributions from aliased out-of-phase peaks. This work extends the spCSI sequence by incorporating double spin-echo radiofrequency (RF) pulses to eliminate the need for phase correction and obtain high quality spectra in magnitude mode. The sequence also provides an added benefit of attenuating signal from flowing spins, which can otherwise contaminate signal in the organ of interest. The refocusing pulses can potentially lead to a loss of hyperpolarized magnetization in dynamic imaging due to flow of spins through the fringe field of the RF coil, where the refocusing pulses fail to provide complete refocusing. Care must be taken for dynamic imaging to ensure that the spins remain within the B 1 -homogeneous sensitive volume of the RF coil.
Bioreactor for quantification of cell metabolism by MR-hyperpolarization
Magnetic resonance (MR)-hyperpolarization based on dynamic nuclear polarization provides a strongly increased signal intensity allowing real-time metabolic spectroscopic imaging. The MR-hyperpolarization technique is, however, still limited by low signal when applied to cells in culture. To overcome this challenge we propose an integrated bioreactor and radio frequency coil system optimized to enhance signal sensitivity. The system allows 13C MR-hyperpolarization-based quantification of metabolic flux in cells grown in a 3D-printed scaffold. The scaffold is designed to enhance the cell density by providing a large surface area for accelerated growth and at the same time provides a controlled culture environment in terms of nutrient flow, oxygen supply and minimal disturbance of the cells. This study demonstrates that a bioreactor optimized for hyperpolarized 13C magnetic resonance spectroscopy in scaffolds can be used to assess fast metabolic fluxes in cultivated cells.
NMR in Biomedicine, 2019
Hyperpolarized-13 C MRI takes advantage of the unprecedented 50,000x SNR enhancement to interrogate cancer metabolism in patients and animals. It can measure the pyruvate-to-lactate conversion rate, k PL , a metabolic biomarker of cancer aggressiveness and progression. Therefore, it is crucial to evaluate k PL reliably. In this study, three sequence components and parameters that modulate k PL estimation were identified and investigated in model simulations and through in vivo animal studies using several specifically designed pulse sequences. These factors included a magnetization spoiling effect due to RF pulses, a crusher gradient-induced flow suppression, and intrinsic image weightings due to relaxation. Simulation showed the RF-induced magnetization spoiling can be substantially improved using an inputless k PL fitting. In vivo studies found a significantly higher apparent k PL with an additional gradient that leads to flow suppression (k PL,FID-Delay,Crush /k PL,FID-Delay = 1.37±0.33, P<0.01, N=6), which agrees with simulation outcomes (12.5% k PL error with Δv=40cm/s), indicating that the gradients predominately suppressed flowing pyruvate spins. Significantly lower k PL was found using a delayed FID acquisition versus a minimum-TE version (k PL,FID-Delay /k PL,FID = 0.67±0.09, P<0.01, N=5), and the lactate peak had broader linewidth than pyruvate (Δω lactate /Δω pyruvate = 1.32±0.07, P<0.00001, N=13). This illustrated that lactate's shorter T2* than pyruvate can affect calculated k PL values. We also found an FID sequence yielded significantly lower k PL versus a double spin-echo sequence that includes spin-echo spoiling, flow suppression from crusher gradients, and more T2weighting (k PL,DSE /k PL,FID = 2.40±0.98, P<0.0001, N=7). In summary, the pulse sequence, as well as its interaction with pharmacokinetics and tissue microenvironment can impact and be optimized for the measurement of k PL. The data acquisition and analysis pipelines can work synergistically to provide more robust and reproducible k PL measures for future preclinical and clinical studies.
Metabolic Reactions Studied by Zero- and Low-Field Nuclear Magnetic Resonance
arXiv (Cornell University), 2022
State-of-the-art magnetic resonance imaging uses hyperpolarized molecules to track metabolism in vivo, but large superconducting magnets are required, and the strong magnetic fields largely preclude measurement in the presence of conductive materials and magnify problems of magnetic susceptibility inhomogeneity. Operating at zero and low field circumvents these limitations, but until now has not been possible due to limited sensitivity. We show that zero-and low-field nuclear magnetic resonance can be used for probing two important metabolic reactions: the conversion of hyperpolarized fumarate to malate and pyruvate to lactate. This work paves the way to a heretofore unexplored class of biomedical imaging applications.
In vivo magnetic resonance of hyperpolarized [13C1]pyruvate: metabolic dynamics in stimulated muscle
American Journal of Physiology-Endocrinology and Metabolism, 2013
The metabolic status of muscle changes according to the energetic demands of the organism. Two key regulators of these changes include exercise and insulin, with exercise eliciting catabolic expenditure within seconds and insulin enabling anabolic energy investment over minutes to hours. This study explores the potential of time-resolved hyperpolarized dynamic13C spectroscopy to characterize the in vivo metabolic phenotype of muscle during functional and biochemical insulin-induced stimulation of muscle. Using [13C1]pyruvic acid as a tracer, we find that despite the different time scales of these forms of stimulation, increases in pyruvate label transport and consumption and concomitant increases in initial rates of the tracer metabolism to lactate were observed for both stimuli. By contrast, rates of tracer metabolism to labeled alanine increased incrementally for insulin but remained unchanged following exercise-like muscle stimulation. Kinetic analysis revealed that branching of ...